Clinical Utility of Intravascular Ultrasound (IVUS) in Carotid Artery Interventions: A Systematic Review and Meta-analysis.

BACKGROUND: Carotid plaque morphology plays an important role in determining outcome of carotid artery stenting (CAS). Intravascular ultrasound (IVUS) and its extension VH (Virtual Histology)-IVUS evaluate plaque characteristics in real time and guide decision making during stenting. To date, there is no consensus about indications of IVUS and its validated methods. This systematic review and meta-analysis aims to evaluate the clinical utility of IVUS in carotid artery interventions (CAS) and develop a future consensus for research and practice parameters. METHODS: A systematic review and meta-analysis was performed of the English literature articles published till February 2021. Studies reporting on IVUS parameters and findings and also its performance compared with other imaging modalities were included in review. Pooled prevalence with 95% confidence intervals (CI) was calculated. The statistical analysis was conducted in R version 3.6.2. RESULTS: A total of 2015 patients from 29 studies were included. Proportional meta-analysis was performed on 1566 patients from 11 studies. In 9 studies, stroke/transient ischemic attack (TIA) had a pooled prevalence of 4% (95% CI 3%-5%) while asymptomatic stroke had a pooled prevalence of 46% (95% CI 31%-62%) in 4 studies following IVUS. Two studies reported that IVUS detected more plaque protrusion compared with angiography (n=33/396 vs 11/396). IVUS led to stent type or size change in 8 of 48 cases which were missed on angiography in 3 other studies. Concordance between VH-IVUS and true histology was good at 80% to 85% reported in 2 studies. CONCLUSIONS: This systematic review and meta-analysis showed, though IVUS fared better to computed tomography (CT)/magnetic resonance (MR) angiography for better stent selection during CAS, with low to moderate risk of bias in the studies included. However, large scale, preferably randomized controlled studies are needed to predict its role in determining clinical outcome.

Neuronal specificity of alpha-synuclein toxicity and effect of Parkin co-expression in primates.

Recombinant adeno-associated viral (rAAV) vector-mediated overexpression of alpha-synuclein (alphaSyn) protein has been shown to cause neurodegeneration of the nigrostriatal dopaminergic pathway in rodents and primates. Using serotype-2 rAAV vectors, we recently reported the protective effect of Parkin on alphaSyn-induced nigral dopaminergic neurodegeneration in a rat model. Here we investigated the neuronal specificity of alphaSyn toxicity and the effect of Parkin co-expression in a primate model. We used another serotype (type-1) of AAV vector that was confirmed to deliver genes of interest anterogradely and retrogradely to neurons in rats. The serotype-1 rAAV (rAAV1) carrying alphaSyn cDNA (rAAV1-alphaSyn), and a cocktail of rAAV1-alphaSyn and rAAV1 carrying parkin cDNA (rAAV1-parkin) were unilaterally injected into the striatum of macaque monkeys, resulting in protein expression in striatonigral GABAergic and nigrostriatal dopaminergic neurons. Injection of rAAV1-alphaSyn alone decreased tyrosine hydroxylase immunoreactivity in the striatum compared with the contralateral side injected with a cocktail of rAAV1-alphaSyn and rAAV1-parkin. Immunostaining of striatonigral GABAergic neurons was similar on both sides. Overexpression of Parkin in GABAergic neurons was associated with less accumulation of alphaSyn protein and/or phosphorylation at Ser129 residue. Our results suggest that the toxicity of accumulated alphaSyn is not induced in non-dopaminergic neurons and that the alphaSyn-ablating effect of Parkin is exerted in virtually all neurons in primates.

Parallel neural networks for learning sequential procedures.

Recent studies have shown that multiple brain areas contribute to different stages and aspects of procedural learning. On the basis of a series of studies using a sequence-learning task with trial-and-error, we propose a hypothetical scheme in which a sequential procedure is acquired independently by two cortical systems, one using spatial coordinates and the other using motor coordinates. They are active preferentially in the early and late stages of learning, respectively. Both of the two systems are supported by loop circuits formed with the basal ganglia and the cerebellum, the former for reward-based evaluation and the latter for processing of timing. The proposed neural architecture would operate in a flexible manner to acquire and execute multiple sequential procedures.

Uphill energy transfer in a chlorophyll d-dominating oxygenic photosynthetic prokaryote, Acaryochloris marina.

The steady-state fluorescence properties and uphill energy transfer were analyzed on intact cells of a chlorophyll (Chl) d-dominating photosynthetic prokaryote, Acaryochloris marina. Observed spectra revealed clear differences, depending on the cell pigments that had been sensitized; using these properties, it was possible to assign fluorescence components to specific Chl pigments. At 22 degrees C, the main emission at 724 nm came from photosystem (PS) II Chl d, which was also the source of one additional band at 704 nm. Chl a emissions were observed at 681 nm and 671 nm. This emission pattern essentially matched that observed at -196 degrees C, as the main emission of Chl d was located at 735 nm, and three minor bands were observed at 704 nm, 683 nm, and 667 nm, originating from Chl d, Chl a, and Chl a, respectively. These three minor bands, however, had not been sensitized by carotenoids, suggesting specific localization in PS II. At 22 degrees C, excitation of the red edge of the absorption band (which, at 736 nm, was 20 nm longer than the absorption maximum), resulted in fluorescence bands of Chl d at 724 nm and of Chl a at 682 nm, directly demonstrating an uphill energy transfer in this alga. This transfer is a critical factor for in vivo activity, due to an inversion of energy levels between antenna Chl d and the primary electron donor of Chl a in PS II.

Molecular structure, localization and function of biliproteins in the chlorophyll a/d containing oxygenic photosynthetic prokaryote Acaryochloris marina.

We investigated the localization, structure and function of the biliproteins of the oxygenic photosynthetic prokaryote Acaryochloris marina, the sole organism known to date that contains chlorophyll d as the predominant photosynthetic pigment. The biliproteins were isolated by means of sucrose gradient centrifugation, ion exchange and gel filtration chromatography. Up to six biliprotein subunits in a molecular mass range of 15.5-18.4 kDa were found that cross-reacted with antibodies raised against phycocyanin or allophycocyanin from a red alga. N-Terminal sequences of the alpha- and beta-subunits of phycocyanin showed high homogeneity to those of cyanobacteria and red algae, but not to those of cryptomonads. As shown by electron microscopy, the native biliprotein aggregates are organized as rod-shaped structures and located on the cytoplasmic side of the thylakoid membranes predominantly in unstacked thylakoid regions. Biochemical and spectroscopic analysis revealed that they consist of four hexameric units, some of which are composed of phycocyanin alone, others of phycocyanin together with allophycocyanin. Spectroscopic analysis of isolated photosynthetic reaction center complexes demonstrated that the biliproteins are physically attached to the photosystem II complexes, transferring light energy to the photosystem II reaction center chlorophyll d with high efficiency.

Fluorescence properties of chlorophyll d-dominating prokaryotic alga, acaryochloris marina: studies using time-resolved fluorescence spectroscopy on intact cells

Antenna components and the primary electron donor of the photosystem (PS) II in the Chlorophyll (Chl) d-dominating prokaryote, Acaryochloris marina, were studied using time-resolved fluorescence spectroscopy in the ps time range. By selective excitation of Chl a or Chl d, differences in fluorescence properties were clearly resolved. At physiological temperature, energy transfer was confirmed by a red shift of emission maximum among PS II antenna components, and the equilibrium of energy distribution among Chl a and Chl d was established within 30 ps. A fluorescence component that can be assigned to delayed fluorescence (DF) was observed at 10 ns after the excitation; however, it was not necessarily resolved by the decay kinetics. At -196 degrees C, a red shift of emission maximum was reproduced but the equilibrium of energy distribution was not detected. DF was resolved in the wavelength region corresponding to Chl a by spectra and by decay kinetics. The lifetime of the DF was estimated to be approx. 15 ns, and the peaks were located at 681 and 695 nm, significantly shorter wavelengths than those of Chl d. These findings strongly suggest that an origin of DF is Chl a, and Chl a is most probably the primary electron donor in the PS II reaction center (RC). These results indicate that the constitution of PS II RC in this alga is essentially identical to that of other oxygenic photosynthetic organisms.

Coincident stimulation of convergent cortical inputs enhances immediate early gene induction in the striatum.

The effect of coincident stimulation of convergent corticostriatal inputs was analyzed by the induction of immediate early genes in striatal neurons. Cortical motor areas were stimulated through implanted electrodes in awake, behaving rats, and the induction of the mRNAs encoding the immediate early genes (IEGs) c-fos and arc was analyzed in the striatum with in situ hybridization histochemistry. In the first experiment, unilateral stimulation of the medial agranular cortex, orofacial region of the lateral agranular cortex or the forelimb region of the lateral agranular cortex resulted in IEG induction in the striatum, which was restricted to the topographically related area receiving input from the stimulated cortical area. In a second experiment, stimulation parameters were altered, including frequency, number of pulses/train, and number of trains/s. These parameters did not have a significant effect on IEG induction. Notably, in some cases, in which there was IEG induction not only in the stimulated cortical region, but also in the homologous area in the contralateral hemisphere, very robust IEG induction was observed in the striatum. In a third experiment, the orofacial regions of the lateral agranular cortex of both hemispheres were stimulated coincidently. All of these animals showed robust striatal IEG induction. This IEG induction was attenuated by pretreatment with an NMDA antagonist MK-801. In a fourth experiment, we tested whether the coincidence of bilateral cortical stimulation contributed to the efficacy of striatal IEG induction. Either alternating stimulation or coincident stimulation of non-homologous cortical regions produced significantly lower striatal IEG induction than obtained with coincident stimulation of homologous cortical areas. Enhanced striatal IEG induction occurred in indirect striatal neurons, labeled with enkephalin, but was also present in a large number of enkephalin-negative neurons, most of which are likely direct pathway neurons. These results suggest that regional and temporal convergence of cortical inputs enhances striatal IEG induction.

Purification and characterization of hydrogenase from the marine green alga, Chlorococcum littorale.

Hydrogenase from the marine green alga, Chlorococcum littorale, was purified 1485-fold, resulting in a specific activity for hydrogen evolution of 75.7 micromol/min/mg of protein at 25 degrees C, using reduced methyl viologen as an electron donor. The K(m) value for methyl viologen was 0.5 mM. The purity of the enzyme was judged by native PAGE. The molecular weight was estimated to be 55 kDa by SDS-PAGE, and 57 kDa by gel filtration. The optimum temperature and pH value for hydrogen evolution were 50 degrees C and 7.5, respectively. The partially purified hydrogenase catalyzed hydrogen evolution from ferredoxin that had been isolated from the same cells, but not from NADH or NADPH. The K(m) value for ferredoxin was 0.68 microM. The enzyme was extremely oxygen sensitive, losing over 95% of its activity upon exposure to air within minutes, even at 4 degrees C. Two peptide fragments were obtained from the hydrogenase protein digested enzymatically, and their amino acid sequences were determined. No significant homology was found to any other known sequences of hydrogenases.

Isolation and characterization of biliprotein aggregates from Acaryochloris marina, a Prochloron-like prokaryote containing mainly chlorophyll d.

Phycobiliprotein aggregates were isolated from the prokaryote Acaryochloris marina, containing chlorophyll d as major pigment. In the electron microscope the biliprotein aggregates appear as rod-shaped structures of 26.0 x 11.3 nm, composed of four ring-shaped subunits 5.8 nm thick and 11.7 nm in diameter. Spectral data indicate that the aggregates contain two types of biliproteins: phycocyanin and an allophycocyanin-type pigment, with very efficient energy transfer from the phycocyanin- to allophycocyanin-type constituent. The chromophore-binding polypeptides of the pigments have apparent molecular masses of 16.2 and 17.4 kDa. They crossreact with antibodies against phycocyanin and allophycocyanin from a red alga.

Light-harvesting in Acaryochloris marina--spectroscopic characterization of a chlorophyll d-dominated photosynthetic antenna system.

Oxygenic photosynthesis of the prokaryote Acaryochloris marina involves chlorophyll d (Chl d) as the major pigment [Miyashita et al. (1996) Nature 383, 402]. Four spectral forms of Chl d (peak wavelengths: 694, 714, 726 and 740 nm) are resolvable by low-temperature absorption spectroscopy on intact cells. Based on fluorescence spectra (at 290 K and 77 K) and on analysis of fluorescence induction curves we conclude: (1) excitation energy is efficiently transferred between the various spectral forms of Chl d and the PS II reaction center; (2) Chl d serves as a light-harvesting pigment for both, Photosystem II (PS II) and PS I; (3) excitation energy transfer between PS II units occurs.

A study of dose escalation of teniposide (VM-26) plus cisplatin (CDDP) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced small cell lung cancer.

A dose escalation study of teniposide (VM-26) plus cisplatin (CDDP) was carried out using recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 46 previously untreated patients with advanced small cell lung cancer (SCLC). The dose of CDDP was 80 mg/m2/day intravenously (i.v.) (day 1) and VM-26 was escalated from 60 mg/m2/day to 80, 100 and 120 mg/m2/day i.v. x 5 days for four cycles. The dose of rhG-CSF was 90 micrograms/m2/day subcutaneously for 13 days. The feasibility of the regimen at the starting dose level of VM-26 with or without rhG-CSF was initially examined in 10 patients chosen through random allocation. WHO grade 4 neutropenia was observed in 17% (three out of 18 courses) of patients in the rhG-CSF group and in 63% (12 out of 19 courses) of the control group (P < 0.01). The number of patients with febrile episodes (> 38 degrees C) over the four courses of chemotherapy was 1 in the rhG-CSF group and 4 in the control group. According to these results, all 36 patients received rhG-CSF in the dose escalation stage. The incidence of WHO grade 4 neutropenia at the dose levels of 60, 80, 100 and 120 mg/m2/day of VM-26 was 66, 57, 76 and 85%, respectively (P > 0.1). The incidence of grade 4 thrombocytopenia was 19, 31, 18 and 46%, respectively (P > 0.1). The overall response rate was 100% in patients with limited stage SCLC and 83% in patients with extensive stage SCLC. The actual administered VM-26 dose per week at the dose level of 100 mg/m2/day was 1.6-fold higher than the planned starting dose (60 mg/m2/day) per week. At the dose level of 120 mg/m2/day, 50% of patients developed WHO grade 4 leucopenia, which lasted longer than 1 week and 67% of the patients had WHO grade 3 or 4 diarrhoea. At this same dose, all patients had at least one febrile episode (> 38 degrees C), and 1 patient died of cerebral bleeding with severe thrombocytopenia. The median survival time of all patients was 451 days (411 days, extensive disease; 497 days, limited disease). VM-26 plus CDDP with rhG-CSF was active in previously untreated patients with SCLC. The recommended dose of VM-26 in combination with CDDP for a phase II study is 100 mg/m2/day for 5 days with rhG-CSF support.

Inhibition of photosynthesis by intracellular carbonic anhydrase in microalgae under excess concentrations of CO(2).

When cells of Chlorococcum littorale that had been grown in air (air-grown cells) were transferred to extremely high CO(2) concentrations (>20%), active photosynthesis resumed after a lag period which lasted for 1-4 days. In contrast, C. littorale cells which had been grown in 5% CO(2) (5% CO(2)-grown cells) could grow in 40% CO(2) without any lag period. When air-grown cells were transferred to 40% CO(2), the quantum efficiency of PS II (Phi(II)) decreased greatly, while no decrease in Phi(II) was apparent when the 5% CO(2)-grown cells were transferred to 40% CO(2). In contrast to air-grown cells, 5% CO(2)-grown cells showed neither extracellular nor intracellular carbonic anhydrase (CA) activity. Upon the acclimation of 5% CO(2)-grown cells to air, photosynthetic susceptibility to 40% CO(2) was induced. This change was associated with the induction of CA. In addition, neither suppression of photosynthesis nor arrest of growth was apparent when ethoxyzolamide (EZA), a membrane-permeable inhibitor of CA, had been added before transferring air-grown cells of C. littorale to 40% CO(2). The intracellular pH value (pH(i)) decreased from 7.0 to 6.4 when air-grown C. littorale cells were exposed to 40% CO(2) for 1-2 h, but no such decrease in pH(i) was apparent in the presence of EZA. Both air- and 5% CO(2)-grown cells of Chlorella sp. UK001, which was also resistant to extremely high CO(2) concentrations, grew in 40% CO(2) without any lag period. The activity of CA was much lower in air-grown cells of this alga than those in air-grown C. littorale cells. These results prompt us to conclude that intracellular CA caused intracellular acidification and hence inhibition of photosynthetic carbon fixation when air-grown C. littorale cells were exposed to excess concentrations of CO(2). No such harmful effect of intracellular CA was observed in Chlorella sp. UK001 cells.

Functional characteristics of chlorophyll d-predominating photosynthetic apparatus in intact cells of Acaryochloris marina.

Functional organization of the photosynthetic apparatus in the unique chlorophyll d-predominating prokaryote, Acaryochloris marina, was studied using polarographic measurements of single-turnover flash yields, action spectra and optical cross sections for PS-specific reactions. O(2) evolution was indicative of PS II activity, while reversible photoinhibition of respiratory O(2) uptake under aerobic conditions in the presence of DCMU and H(2) photoevolution by anaerobically adapted cells were the indicatives of PS I activity. O(2) evolution in the cells upon single-turnover flashes followed the normal S-state cycle with a period-4 oscillation. Analysis of action spectra for the partial reactions of photosynthesis revealed that: (1) distinct spectral forms of Chl d are nonuniformly distributed between PS I and PS II, e.g. Chl d-695 and Chl d-735 are preferentially located in PS II and PS I, respectively; (2) a minor fraction of Chl a in the cells belongs mostly to PS II; (3) biliproteins transfer excitation energy both to PS II and, with a lower efficiency, PS I; (4) the efficiency of energy transfer from biliproteins to PS II depends on the light quality growth conditions and is larger in white light (WL)-grown cells compared to the red light (RL)-grown cells. Content of functional O(2) evolving PS II centers decreases 2 times in the RL-grown cells relative to the WL-grown cells, whereas content of competent PS I centers involved in photoinhibition of respiration remains almost the same in both the cultures. The effective antenna size of PS I was estimated to be 80-90 Chl d including 3-10 molecules absorbing at 735 nm. The effective optical cross-section of PS II corresponded to 90-100 Chl d and, presumably, 4 Chl a + 2 Pheo a [Mimuro et al. (1999) Biochim Biophys Acta 1412: 37-46]. Optical cross-section measurements indicated that the functional PS II units of A. marina attach one rod of four hexameric units of biliproteins.

Allergic bronchopulmonary aspergillosis due to Aspergillus oryzae.

A 19-year-old female student with allergic bronchopulmonary aspergillosis (ABPA) due to Aspergillus oryzae is reported. This organism was used for fermentation starter to make soybean paste in her father's workshop adjacent to the home where she lived. ABPA might be considered an occupational disease in certain situations.

Corticostriatal projections from distal and proximal forelimb representations of the monkey primary motor cortex.

Corticostriatal projections from one distal and two proximal subregions in the forelimb representation of the primary motor cortex (MI) were examined in the macaque monkey. The distal and proximal subregions in the anterior bank of the central sulcus (distal and proximal-bank subregions) and the proximal subregion in the surface of the precentral gyrus (proximal-surface subregion) of the MI were identified using intracortical microstimulation. Different anterograde tracers were then injected into two of these three forelimb subregions of the MI. In the ipsilateral putamen, the distribution areas of corticostriatal fibers from the distal, proximal-bank and proximal-surface subregions were arranged from ventrolateral to dorsomedial in this order. These corticostriatal input zones were largely segregated from one another.

Myeloma manifesting as a large jugular tumor: case report.

The authors report a case of cranial plasmacytoma with multiple myelomas and palsy of the lower cranial nerves. The osteolytic lesion adjacent to the jugular foramen was demonstrated by an angiogram to be exceedingly hypervascular, with arteriovenous shunting resembling that seen in paragangliomas. Forty-five cases of cranial and intracranial plasmacytoma from the literature were reviewed. The findings indicate that a cranial plasmacytoma commonly appears to be a hypervascular tumor, whereas most dural tumors or intraparenchymal tumors have poor vascularity.

Histopathological study of balloon embolization: silicone versus latex.

Bilateral, symmetrical, experimental aneurysms were produced with anastomosed vein flap in the carotid arteries of 24 mongrel dogs. Aneurysms were occluded with latex or silicone balloons on each side and observed angiographically from 2 weeks to 2 months. A histopathological study was performed subsequently using light and scanning electron microscopy. Rupture after balloon embolization occurred in five aneurysms; all of which were incompletely occluded by a silicone balloon. On subsequent angiograms, four silicone balloons and one latex balloon were found to have migrated into the aneurysm, resulting in aneurysmal expansion. Parent artery occlusion was more common with latex balloons than silicone balloons. Histopathologically, residual fresh thrombi, decreased proliferation of fibroblasts within the aneurysmal cavity, and poor endothelialization were present around the silicone balloon. These results suggest that the intra-aneurysmal organization, as seen in the aneurysm occluded by the silicone balloon, will be delayed because the balloon is not fixed within the aneurysm, and that this free-floating and rotating balloon causes repeated trauma to the aneurysm wall, contributing to subsequent enlargement and rupture of the aneurysm. The superior antithrombogenic nature of silicone may be responsible for the bias of such phenomena toward the silicone balloon.

An intracranial mass lesion in systemic xanthogranulomatosis: case report.

The authors describe a 42-year-old woman with systemic xanthogranulomatosis and bilateral intraorbital tumors, who subsequently developed multiple lesions of the intracranial dura mater, spinal cord, retroperitoneum, pericardium, and mediastinum. Systemic xanthogranulomatosis is histologically similar to systemic Weber-Christian disease, except for the absence of subcutaneous panniculitis. Immunohistochemical studies suggest that this clinical entity can be differentiated from histiocytosis X, because foamy cells in systemic xanthogranulomatosis demonstrate macrophages but not T-zone histiocyte markers. Differentiation of this disease from other intracranial xanthogranulomas and treatment are discussed.

Evaluation of pressure changes in feeding arteries during embolization of intracerebral arteriovenous malformations.

The pressure in 47 arteries feeding 21 arteriovenous malformations (AVM's) was investigated during transarterial embolization using a Tracker-18 microcatheter. On average, systolic pressure increased by 22 mm Hg. In AVM's with single or few feeders, embolization was usually achieved well; in contrast, giant AVM's with multiple feeders and a large arteriovenous shunt were poorly embolized. However, large AVM's with well-demarcated components may be reduced by embolization to an appropriate size for surgery or stereotactic radiation therapy. It was found that the feeding artery pressure increased significantly more in well-embolized than in poorly embolized cases. Measurements of the feeding artery pressure clarified the hemodynamics of AVM's and facilitated more successful embolization.

Endovascular trapping of giant serpentine aneurysms by using Guglielmi detachable coils: successful reduction of mass effect. Report of two cases.

Giant serpentine aneurysms (GSAs) are defined as partially thrombosed giant aneurysms with persistent serpentine vascular channels. Surgical management of these rare lesions is difficult because of their large size, complex structure, and unique hemodynamics. The authors report two cases of patients harboring GSAs with mass effect, which were managed effectively with endovascular treatment. The first patient was a 48-year-old man who presented with left homonymous hemianopsia caused by a GSA involving the terminal portion of the right internal carotid artery. The second patient, a 10-year-old boy, presented with tetraparesis from compression of the cervicomedullary junction by a GSA of the right vertebral artery. In each case, after confirming collateral flow by temporarily occluding the proximal artery, the aneurysm was trapped by placement of Guglielmi detachable coils at the sites at which the serpentine channels entered and exited the aneurysm. The midportion of each channel was isolated completely without packing, to maximize resorption of the devascularized mass. Mass effect and clinical symptoms rapidly improved in both cases, with no associated morbidity. We recommend endovascular trapping as a safe and effective therapeutic option for GSAs.